Central action of narcotic analgesics. Part III. The role of endogenous noradrenaline in hyperactivity induced by morphine or fentanyl in mice.

Hyperactivity produced in mice with morphine or fentanyl, and methylamphetamine was antagonized by naloxone. The depression of locomotor activity induced by codeine was practically unchanged by the opiate antagonist. L-DOPA did not restore the stimulatory action of morphine and fentanyl in reserpinized mice. The hyperactivity produced by morphine and fentanyl was abolished in mice treated with alpha-methyl-p-tyrosine, but this was restored by L-DOPA administration. Agents inhibiting the central noradrenaline receptors, phentolamine, phenoxybenzamine, and aceperone, prevented or even reversed the locomotor stimulatory action of morphine and fentanyl. Pimozide did not affect the increase of locomotor activity produced by morphine, but depressed that induced by fentanyl. Haloperidol, used in a dose which did not affect the locomotor activity of mice, completely blocked or even reversed the stimulatory action of morphine and fentanyl, and potentiated the depression of locomotor activity produced by pentazocine and codeine. Diethyldithiocarbamate significantly depressed, but did not inhibit completely the stimulatory action of morphine and fetanyl. The stimulatory action of methylamphetamine was also significantly depressed. It seems that the stimulatory effect of morphine and fentanyl depends on the release of endogenous noradrenaline.